This project continues into its second year of studies on the origin, mode of action, and metabolism of gamma-hydroxybutyrate, (GHB), a compound which is a normal constituent of mammalian brain and which is of increasing pharmacological interest. When administered in pharamcological doses, GHB produces a flattening of the EEG, a reversible trance-like state and a profound depression of cerebral glucose utilization. This compound is being used clinically in Europe as an anesthetic adjuvant. Preliminary trials indicate that it is effective in the treatment of nacrolepsy and may be of use in the treatment of stroke. An enzyme capable of metabolizing GHB has been found in tissues such as liver and kidney as well as the brain. This enzyme, and NADP+-linked alcohol oxido-reductase which interconverts GHB and succinic semialdehyde, has been purified from hamster liver and partially purified from hamster brain. Studies completed on this enzyme include substrate specificity, enzyme kinetics, molecular weight determination, and inhibition studies with the anticonvulsant agents, diphenylhydantoin, amobarbital, and valproate.